The concomitant use of Norco (Hydrocodone and Acetaminophen) tablets and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of the hydrocodone from Norco, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of this drug and both CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of Norco (Hydrocodone and Acetaminophen) is achieved.

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the Norco plasma concentration will decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to Norco (Hydrocodone with Acetaminophen) tablets.

If concomitant use is necessary, consider dosage reduction of Norco until stable drug effects are achieved. Follow patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is
discontinued, consider increasing the Norco (Hydrocodone with Acetaminophen) dosage until stable drug effects are achieved. Follow for signs or symptoms of opioid withdrawal.

Inducers of CYP3A4

The concomitant use of Norco and CYP3A4 inducers, such as carbamazepine, rifampin, and phenytoin, can decrease the plasma concentration of Norco (Hydrocodone, Acetaminophen) tablets, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to this medicine.

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the Norco (Hydrocodone, Acetaminophen) plasma concentration will increase, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

If concomitant use is necessary, consider increasing the Norco (Hydrocodone, Paracetamol) dosage until stable drug effects are achieved.

Follow the patient for signs and symptoms of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Norco (Hydrocodone Bitartrate and Acetaminophen) tablets dosage reduction and follow for signs of respiratory depression.

Benzodiazepines and Other CNS Depressants

Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, such as benzodiazepines and other anxiolytics, sedative hypnotics, tranquilizers, general anesthetics, muscle relaxants, antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation.

Serotonergic Drugs

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., trazodone, mirtazapine, tramadol), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome.

If concomitant use is warranted, carefully follow the patient, particularly during treatment initiation and dose adjustment. Discontinue Norco (Hydrocodone Bitartrate with Acetaminophen) tablets if serotonin syndrome is suspected.

Monoamine Oxidase Inhibitors (MAOIs)

The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, or linezolid, may manifest as serotonin syndrome, or opioid toxicity (e.g., respiratory depression, coma).

The use of Norco (Hydrocodone Bitartrate and Acetaminophen) tablets is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of Norco (Hydrocodone Bitartrate and Acetaminophen) and/or precipitate withdrawal symptoms.

Advise patient to avoid concomitant use of these drugs.

Muscle Relaxants

Norco (Hydrocodone Bitartrate and Paracetamol) may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

If concomitant use is warranted, monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Norco (Hydrocodone Bitartrate with Acetaminophen) tablets and/or the muscle relaxant as necessary.

Diuretics

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.

If concomitant use is warranted, follow patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs

The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

If concomitant use is warranted, follow patients for signs and symptoms of urinary retention or reduced gastric motility when Norco (Hydrocodone Bitartrate with Acetaminophen) are used concomitantly with anticholinergic drugs.